Inhibitory Effect of (−)‐Epigallocatechin‐3‐Gallate on Lipid Accumulation of 3T3‐L1 Cells

Abstract

MOON, HYUN-SEUK, CHUNG-SOO CHUNG, HONG-GU LEE, TAE-GYU KIM, YUN-JAIE CHOI, AND CHONG-SUCHO. Inhibitory effect of (Ϫ)-epigallocatechin-3-gallate on lipid accumulation of 3T3-L1 cells. Obesity. 2007;15:2571-2582. Objective: The objective of this study was to investigate the molecular mechanisms underlying the attenuating effect of (Ϫ)-epigallocatechin-3-gallate (EGCG) on proliferation and lipid accumulation of 3T3-L1 cells, with a focus on the duration of EGCG treatment. Research Methods and Procedures: Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay and diamidino-2-phenylindole staining. The anti-adipogenic effect of EGCG on 3T3-L1 cells was analyzed by glycerol-3-phosphate dehydrogenase activity and Oil red O staining. Western blot analysis was used to detect adenosine monophosphate-activated protein kinase (AMPK) activation and phosphorylation of its substrate, acetyl-CoA carboxylase (ACC), and expression of insulin (INS) receptor, INS receptor substrate-1 (IRS-1), and adipocyte marker proteins. Results: Exposure to EGCG during the early period of adipogenesis (7 days) was sufficient to prevent lipid accumulation. During this period, EGCG greatly decreased expression of the adipocyte marker proteins peroxisome proliferator-activated receptor ␥2 (PPAR␥2) and liver X receptor (LXR)-␣. Furthermore, EGCG significantly induced generation of reactive oxygen species (ROS), which led to AMPK activation, and these effects were eliminated by N-acetylcysteine (NAC) treatment. Also, EGCG increased the tyrosine phosphorylation of INS receptor and INS-1 with increasing incubation time. In contrast, EGCG treatment did not alter glycerol release in the presence or absence of 2Ј,5Ј-dideoxyadenosine (DDA), indicating that EGCG had no effect on lipolysis. Discussion: Our data demonstrate that EGCG decreased cell viability and inhibited differentiation of 3T3-L1 cells in a manner dependent on the duration of treatment. Also, we showed that inhibition of adipocyte differentiation by EGCG was associated with decreased glycerol-3-phosphate dehydrogenase (GPDH) activity accompanied by a strong inhibition of PPAR␥2-induced transcriptional activity. Furthermore, the inhibition of adipocyte differentiation by EGCG involved generation of ROS and activation of AMPK.

Boysenberry Polyphenols Suppressed Elevation of Plasma Triglyceride Levels in Rats

“…Certain polyphenol components were thought to express their anti-obesity effect by modulating various factors related to lipid accumulation after being absorbed into adipose tissues. Tea catechins have been shown to increase acyl-CoA oxidase (5,23) and (2)-epigallocatechin-3-gallate-inhibited lipid accumulation in 3T3-L1 cells (24). Anthocyanins in blueberry also ameliorated serum leptin levels (25) and authentic cyanidin 3-O-glucoside suppressed lipogenesis components at the mRNA level (26).…”

Kaempferitrin improves meat quality of broiler chickens

“…Oxidative stress limits cholesterol outflow by inhibiting its gene expression (Marcil et al, 2006). Antioxidant drug probucol can decrease the level of ANGPTL3 (Moon et al, 2007). It is probable that kaempferitrin decreased expression of ANGPTL3 by inhibiting lipid peroxidation, which in turn resulted in the beneficial effect of kaempferitrin on meat quality.…”

“…Improved antioxidative status in the living animal and increased oxidative stability of the raw product are beneficial to the consumer and the processing industry (Jiang et al, 2007). Besides, oxidative stress induces the expression of ANGPTL3 (Marcil et al, 2006;Moon et al, 2007;Miida et al, 2008). Therefore, the impairment of ANGPTL3 on meat quality might be related to oxidative stress.…”

Pathogenic obesity and nutraceuticals

“…In one study, administration of EGCG to the diets of high-fat fed rats abrogated the development of glucose intolerance with a concomitant increase in PPARg gene expression; however, contrastingly, administration of green tea suppressed PPARg gene expression (131) . In 3T3-L1 cells, investigations have attributed the anti-obesity effects of EGCG to its ability to induce adipocyte apoptosis and inhibit adipocyte differentiation and proliferation, through down-regulation of PPARg and C/EBPa (132)(133)(134) . The concentrations used in these studies ranged from 0 to 200 mM; however, one study found that EGCG administration at 0 .…”